Psychedelics and Suicide-Related Outcomes: A Systematic Review

Background/Objectives: Suicide accounts for 1.4% of global deaths, and the slow-acting nature of traditional treatments for suicide risk underscores the need for alternatives. Psychedelic therapies may rapidly reduce suicide risk. This systematic review evaluates impact of psychedelic therapies on suicide-related outcomes. Methods: A systematic search of MEDLINE, Embase, PsycINFO, and ClinicalTrials.gov was conducted up to November 2024. Results: Four randomized controlled trials (RCTs) evaluated suicidality as a secondary outcome or safety measure, showing significant reductions in suicidal ideation with psilocybin (three studies) and MDMA-assisted therapy (MDMA-AT; one study). Effect sizes, measured by Cohen's d, ranged from =0.52 to 1.25 (p = 0.01 to 0.005), with no safety issues reported. Five additional RCTs assessed suicidality as a safety measure, showing reductions in suicidal ideation with psilocybin (two studies) and MDMA-AT (three studies; p = 0.02 to 0.04). Among 24 non-randomized and cross-sectional studies, results were mixed. Psilocybin (three studies) reduced suicidal ideation, with odds ratios (OR) of 0.40-0.75. MDMA-AT (five studies in PTSD patients) had a pooled effect size of d = 0.61 (95% CI: 0.32-0.89). LSD (six studies) showed increased odds of suicidality, with odds ratios ranging from 1.15 to 2.08. Studies involving DMT (two studies) and multiple psychedelics (three studies) showed mixed results, with DMT studies not showing significant effects on suicidality and studies involving multiple psychedelics showing varying outcomes, some reporting reductions in suicidal ideation and others showing no significant change. Conclusions: The effect of psychedelic therapies on suicide-related outcomes remains inconclusive, highlighting the need for further trials to clarify safety and therapeutic mechanisms.